Cancer is a major cause of death worldwide, being the second-leading cause of death in developed countries, and even the number one cause of death in e.g. Australia, Japan, Korea, Singapore and the male population of the UK and Spain. The number of people who develop cancer each year is increasing. Nevertheless cancer therapy has not managed to decrease cancer mortality in the last three decades.
Autonomous cell growth resulting in tissue invasion and metastasis is the defining feature of all malignant neoplasms. Cancers do not necessarily arise solely as a result of an accelerated rate of cell proliferation. Rather they are the consequence of an imbalance between the rate of cell-cycle progression (cell division) and cell growth (cell mass) on one hand and programmed cell death (apoptosis) on the other.
Resolving the identity of the oncogenic drivers of tumorigenesis and metastatic growth is crucial not only for understanding the pathobiology of cancer, but also for treating patients, as such genes are increasingly being exploited for therapeutic benefit (Herceptin, Avastin, Gleevec). In human cancers, oncogenes are frequently activated by aberrant overexpression resulting from genomic amplification, sequence mutations or promoter hypomethylation. Chromosomal loci that are frequently amplified in cancer, known as amplicons, are thought to be driven by one or more oncogenes, and though many recurrent amplicons have been observed, their oncogenic determinants remain largely unknown. These loci have traditionally been interrogated by cytogenetics techniques such as comparative genomic hybridization (CGH) to assess the extent and frequency of copy number gains, and although this strategy has provided many gene candidates for consideration, the extensive size of the gene lists, together with a paucity of functional information, has limited progress towards oncogene discovery. More frequently, the discovery of oncogenes has been a slow and empirical process—depending mostly on the generation of hypotheses derived from cumulative observations of gene function in different experimental contexts.
It is an object of the present invention to provide means of controlling, including preventing tumorigenesis and of identifying a cell with a predisposition to turn tumorigenic.